Bottom Line:
However, their safety to the health of humans and wildlife remains inconclusive.The results showed that all four substances and the mixtures of CAF with the sweeteners affected development.We found that the ranking of developmental toxicity was SAC > CAF > ASP > SUC, and there was a cumulative effect when CAF was combined with the sweeteners.

ABSTRACTThe use of artificial sweeteners (ASWs) has increased and become more widespread, and consequently ASWs have appeared in aquatic environments around the world. However, their safety to the health of humans and wildlife remains inconclusive. In this study, using medaka embryos (Oryzias latipes), we investigated developmental toxicity of aspartame (ASP) and saccharin (SAC). Since ASWs are often consumed with caffeine (CAF) and CAF with sucrose (SUC), we tested biological activities of these four substances and the mixtures of CAF with each sweetener. The embryos were exposed to ASP at 0.2 and 1.0 mM, SAC at 0.005 and 0.050 mM, CAF at 0.05 and 0.5 mM, or SUC at 29 and 146 mM, starting from less than 5 h post fertilization until hatch. Control embryos were treated with embryo solution only. Several endpoints were used to evaluate embryonic development. Some of the hatchlings were also tested for anxiety-like behavior with the white preference test. The results showed that all four substances and the mixtures of CAF with the sweeteners affected development. The most sensitive endpoints were the heart rate, eye density, and hatchling body length. The hatchlings of several treatment groups also exhibited anxiety-like behavior. We then used the Integrated Biological Response (IBR) as an index to evaluate the overall developmental toxicity of the substances. We found that the ranking of developmental toxicity was SAC > CAF > ASP > SUC, and there was a cumulative effect when CAF was combined with the sweeteners.

Fig1: Representative images of medaka embryos exposed to saccharin at 0.05 mM (SAC2) or embryo solution only (control) at 1–3 days post fertilization (dpf). The exposures started from less than 5 h post fertilization until hatch. The images were cropped, but their relative proportion was maintained. No other alteration was made. Bar 100 µm

Mentions:
Representative images of the embryos from the control and SAC2 groups are shown in Fig. 1, in which the SAC2-treated embryo appeared to be less developed than the control. The responses of each endpoint are described as follows:Fig. 1

Fig1: Representative images of medaka embryos exposed to saccharin at 0.05 mM (SAC2) or embryo solution only (control) at 1–3 days post fertilization (dpf). The exposures started from less than 5 h post fertilization until hatch. The images were cropped, but their relative proportion was maintained. No other alteration was made. Bar 100 µm

Mentions:
Representative images of the embryos from the control and SAC2 groups are shown in Fig. 1, in which the SAC2-treated embryo appeared to be less developed than the control. The responses of each endpoint are described as follows:Fig. 1

Bottom Line:
However, their safety to the health of humans and wildlife remains inconclusive.The results showed that all four substances and the mixtures of CAF with the sweeteners affected development.We found that the ranking of developmental toxicity was SAC > CAF > ASP > SUC, and there was a cumulative effect when CAF was combined with the sweeteners.

ABSTRACTThe use of artificial sweeteners (ASWs) has increased and become more widespread, and consequently ASWs have appeared in aquatic environments around the world. However, their safety to the health of humans and wildlife remains inconclusive. In this study, using medaka embryos (Oryzias latipes), we investigated developmental toxicity of aspartame (ASP) and saccharin (SAC). Since ASWs are often consumed with caffeine (CAF) and CAF with sucrose (SUC), we tested biological activities of these four substances and the mixtures of CAF with each sweetener. The embryos were exposed to ASP at 0.2 and 1.0 mM, SAC at 0.005 and 0.050 mM, CAF at 0.05 and 0.5 mM, or SUC at 29 and 146 mM, starting from less than 5 h post fertilization until hatch. Control embryos were treated with embryo solution only. Several endpoints were used to evaluate embryonic development. Some of the hatchlings were also tested for anxiety-like behavior with the white preference test. The results showed that all four substances and the mixtures of CAF with the sweeteners affected development. The most sensitive endpoints were the heart rate, eye density, and hatchling body length. The hatchlings of several treatment groups also exhibited anxiety-like behavior. We then used the Integrated Biological Response (IBR) as an index to evaluate the overall developmental toxicity of the substances. We found that the ranking of developmental toxicity was SAC > CAF > ASP > SUC, and there was a cumulative effect when CAF was combined with the sweeteners.